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Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

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ClinicalTrials.gov Identifier: NCT01619280
Recruitment Status : Unknown
Verified June 2012 by Mount Sinai Hospital, Canada.
Recruitment status was:  Recruiting
First Posted : June 14, 2012
Last Update Posted : June 14, 2012
Sponsor:
Information provided by (Responsible Party):
Mount Sinai Hospital, Canada

Study Description
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Brief Summary:

Acute lung injury (ALI) is caused by a wide variety of conditions, but always characterized by hypoxia and non-cardiogenic pulmonary edema. Current treatment of ALI is supportive and treatment of the underlying cause. New therapies to treat severe ALI have not been shown to improve survival, and are limited by financial and logistical resources.

The investigators propose to investigate the role of inhaled sodium nitroprusside (iSNP) in ALI. Sodium nitroprusside (SNP) is a vasodilator. When inhaled, SNP may travel to areas of the lung participating in gas exchange, and cause the blood vessels surrounding these areas to enlarge. This may result in an increase of blood vessels to these areas of the lung, and improve oxygenation. Currently, iSNP has not been studied in the adult population. Therefore, this study is intended to find the safety profile of varying doses of iSNP.


Condition or disease Intervention/treatment Phase
Acute Lung Injury Acute Respiratory Distress Syndrome Sodium Nitroprusside Hypoxia Respiratory Failure Drug: Sodium Nitroprusside Phase 1

Detailed Description:

Acute lung injury (ALI) is a syndrome characterized by acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension. ALI is responsible for significant mortality and morbidity in the critically ill population.

Novel rescue therapies used to support oxygenation in severe ALI include inhaled nitric oxide and high frequency oscillatory ventilation; however, neither have been shown to reduce mortality and both are limited by logistical and financial challenges.

Inhaled sodium nitroprusside (iSNP) is a vasodilator which causes local vasodilation of pulmonary capillaries surrounding functional alveoli, resulting in improved oxygenation by redistributing pulmonary blood flow to areas with better ventilation-perfusion ratios. As iSNP can be administered by a low-cost nebulizer and is relatively inexpensive compared to other novel rescue therapies, this modality may be an alternative therapy for patients with severe hypoxemia. Two pediatric studies support the use of iSNP in ALI; however, iSNP has not been studied in the adult ALI population. To determine whether iSNP can improve oxygenation in adult ALI, the maximum tolerable dose (MTD) must first be determined.

Our study aims to determine the MTD of iSNP in adult ALI through an open-label, non-randomized, single centered, dose escalation study design, whereby subjects will receive iSNP for thirty minutes and have various physiologic variables recorded.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study: The Determination of the Maximum Tolerable Dosage of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
Study Start Date : May 2012
Estimated Primary Completion Date : June 2013
Estimated Study Completion Date : June 2013

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Nebulized sodium nitroprusside Drug: Sodium Nitroprusside
Each subject will receive one of five possible dosages of nebulized sodium nitroprusside. The dosage will be determined by the 3 + 3 dose escalation design. Only a maximum of six patients will be given a particular dosage. Arterial blood gases will be drawn at 0 min, 15 min, 30 min and 45 min during nebulized sodium nitroprusside administration. Vitals signs will be recorded every five minutes. No changes to ventilator settings or vasopressor dosage or fluid administration will be allowed.
Other Name: Nipride, Nitropress


Outcome Measures
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Primary Outcome Measures :
  1. The maximum tolerable dosage of nebulized sodium nitroprusside. This will be determined by the 3 + 3 dose finding design. [ Time Frame: Up to 1 year ]
    Participants will be followed for the duration of the intervention of 45 min. . It is anticipated it will take up to 1 year to recruit the required number of participants to determine the maximum tolerable dose of nebulized sodium nitroprusside.


Secondary Outcome Measures :
  1. The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ]
  2. The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ]
  3. The presence or absence of lactate, and/or methemoglobin. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18
  2. Negative β-hCG in women of child bearing age (age ≤ 50)

  3. Developed ALI within past 72 hours:

    • PaO2/FiO2 < 300;
    • Bilateral infiltrates on CXR;
    • No clinical evidence of elevated left atrial pressure ie. Heart failure as the cause of hypoxia and bilateral infiltrates; and
    • Recognized risk factor for ALI such as: pneumonia, aspiration pneumonitis, acute pancreatitis, massive blood transfusion, or sepsis
  4. FiO2 ≥ 0.5
  5. PEEP ≥ 8 cm H2O
  6. Invasive arterial blood pressure line
  7. Endotracheal intubation or tracheostomy
  8. Conventional mechanical ventilation
  9. Mean Arterial Pressure (MAP) ≥ 65 mmHg with or without use of vasopressors (stable for at least more than 1 hour)
  10. Arterial pH ≥ 7.15

Exclusion Criteria:

  1. Chest tube with active leak (eg. bronchopulmonary fistula),
  2. Prone ventilation, inhaled nitric oxide, inhaled prostacyclin, high frequency oscillatory ventilation,
  3. Lack of consent,
  4. Untreated coarctation of aorta, symptomatic or severe/critical aortic stenosis as documented by echocardiogram or clinical history,
  5. Evidence of increased intracranial pressure (eg. dilated pupils, known intracranial trauma or mass on head CT),
  6. SpO2 <90%,
  7. Contraindication to SNP i.e. hypersensitivity, congenital optic atrophy, tobacco amblyopia,
  8. Active treatment with IV or transdermal nitroglycerin,
  9. G6PD deficiency
  10. CrCl < 30 ml/min or receiving renal replacement therapy, or
  11. Total bilirubin > 68 µmol/L and AST or ALT level 2 times the upper limit of normal.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01619280


Contacts
Contact: Terence Ip, MD terence.ip@utoronto.ca

Locations
Canada, Ontario
Mount Sinai Hospital, University of Toronto Recruiting
Toronto, Ontario, Canada, M5G 1X5
Principal Investigator: Terence Ip, MD         
Principal Investigator: Sangeeta Mehta, MD FRCPC         
Sub-Investigator: Lisa Burry, PharmD         
Sub-Investigator: Cynthia Harris, RRT         
Sub-Investigator: John Traill, RRT         
Sub-Investigator: Niall Ferguson, MD, FRCPC         
Sponsors and Collaborators
Mount Sinai Hospital, Canada
Investigators
Principal Investigator: Sangeeta Mehta, MD FRCPC Department of Critical Care Medicine, University of Toronto
Principal Investigator: Terence Ip, MD Department of Critical Care Medicine, University of Toronto
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier: NCT01619280     History of Changes
Other Study ID Numbers: 10-0102-A
First Posted: June 14, 2012    Key Record Dates
Last Update Posted: June 14, 2012
Last Verified: June 2012

Keywords provided by Mount Sinai Hospital, Canada:
Acute Lung Injury
Acute Respiratory Distress Syndrome
Sodium Nitroprusside
adult
Safety
Dose Finding
Phase 1
 3 + 3 design
Nebulizers and Vaporizers
High-Frequency Ventilation
nitric oxide
lung injury
Pulmonary Gas Exchange
Pulmonary Alveoli

Additional relevant MeSH terms:
Wounds and Injuries
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Respiratory Insufficiency
Hypoxia
Acute Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
 Infant, Premature, Diseases
Infant, Newborn, Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Thoracic Injuries
Nitroprusside
Antihypertensive Agents
Vasodilator Agents
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action